The proposed studies are designed to examine the long term effects of otitis media with effusion acquired during infancy and early childhood. Thses studies will be carried out longitudinally in cohorts of normal neonates and children and will involve careful clinical evaluation, followed by tympanocentesis in appropriate subjects. Sequentially collected samples of serum, heparinized blood, and middle ear aspirates will be examined for the presence of selected bacteria and viruses and for microbial specific antigens. Specific studies will be undertaken to determine the characteristics and functional levels of specific immunologic reactivity in the middle ear. The release of pharmacologic mediators by polymorphonuclear leukocytes and other inflammatory cells observed in the middle ear excudates will also be studied. The laboratory procedures will include routine and some sophisticated microbiologic and immunologic tests. All are currently in use in our laboratories. It is anticipated that the results emanating from these investigations will define the natural history of otitis media in infancy relative to the nature of innate or infection-induced immunologic reactivity, the characteristics of bacterial-viral interation, or the activation of other non-immunologic mechanisms (such as the oxidative metabolites of polymorphonuclear leukocytes) in the middle ear cavity. The studies should determine the factors which predispose to the development of recurrent otitis media or different forms of chronic or persistent otitis media with serous, mucoid or purulent effusions in infancy and childhood. These studies would be essential to the long range goals of management of childhood otitis media namely; the appropriate antimicrobial therapy and eventual development of effective measures of prevention.